Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

Abstract

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5 enhancement of tumor growth and metastasis

“…Gastric cancer is one of the leading causes of cancer-related mortality worldwide (1,2). Patients with gastric cancer are commonly diagnosed at an advanced stage and their median 5-year survival rates are no more than 20% (3).…”

Evidencia en mundo real: revisión de la experiencia clínica en el tratamiento de segunda línea del cáncer gástrico metastásico con ramucirumab

“…Los beneficios que se muestran con el inhibidor del RFGEV-2 ramucirumab, y el inhibidor de tirosina cinasa de VEGFR-2 apatinib, representan un avance en el desarrollo de fármacos antiangiogénicos en el CG metastásico 27,28 . Los futuros protocolos deben investigar la administración de ramucirumab como primera línea en combinación con otros quimioterapéuticos o con una determinación molecular específica; por lo tanto, son aspectos a resolver su utilización como tratamiento de mantenimiento y la secuencia con otros tratamientos activos.…”

Antiangiogenic effects of oridonin

“…More than 90% of deaths from solid tumours are attributable to tumour metastasis [27]. Substantial research has been devoted to determining the effect of angiogenesis on tumour development and progression, and the mechanism of action of angiogenesis inhibitors is different from that of traditional chemotherapeutic agents and radiation therapy, providing them with potential in cancer management [28–31]. Moreover, researchers have focused on the health benefits of natural products that influence some steps in cancer-induced angiogenesis, especially in traditional Chinese medicine [32–34].…”